Adrenal Glomerulosa

I Kojima, H Shibata, E Ogata. (1986). Pertussis toxin blocks angiotensin II-induced calcium influx but not inositol trisphosphate production in adrenal glomerulosa cell. FEBS Lett 204 347-351. 

Balia, T. Hunyadi, L. Baukal, A.J. Catt, K.J. Structures and metabolism of inositol tetrakisphosphates and inositol pentakisphosphate in bovine adrenal glomerulosa cells. J. Biol. Chem., 264, 9386-9390 (1989)... 

Possibly relevant to the natriuretic activity of SK F 38393 is emerging evidence that dopamine may be a physiological regulator of aldosterone synthesis (28). Dopamine receptors in a particulate fraction of calf adrenal glomerulosa cells have been shown to bind 3H-2-amino-1,2,3,4-tetrahydro-6,7-dihydroxynaptha-lene (3H-ADTN) in a specific (displaceable by 10 pM dopamine) saturable manner (29) (Kj, 0.29 mM maximal binding capacity,... 

The 5-HT7 receptors also are expressed in the periphery, where their best characterized function is to mediate relaxation of vascular smooth muscle (397). In particular, 5-HT7 receptors are expressed throughout the gut (398) and stomach (399), as well as in vasculature (400,401). 5-HT7 receptors are also expressed in adrenal glomerulosa cells (402,403) and corneal epithelial cells (404). In the adrenal gland, 5-HT7 receptors stimulate the release of aldosterone from adrenal glomerulosa cells (402,403) by increasing cAMP levels. 

Yet, experiments on changes in intracellular Ca2+ levels in adrenal glomerulosa cells exposed to ACTH or Ang II strongly suggest that hormone receptors may also stimulate Ca2+ channels, and that regulation may be directly by a G protein (Gs ). Glomerulosa cells respond to both hormones by secreting aldosterone. However,... 

An increase in the extracellular K+ concentration from 2 to 8 mM (the limits of the physiological range) leads to a 4-5-fold increase in the rate of aldosterone secretion by the adrenal glomerulosa cell [24,25]. This increase in [K+] leads to a depolarization of the plasma membrane of the cell. This depolarization causes the opening of two types of voltage-dependent Ca2+ channel in this membrane, and thus to a 4-fold increase in the rate of Ca2+ influx. The total cell calcium and the [Ca2+]j both... 

The integrated cellular response of the adrenal glomerulosa cell is determined by the activities of three different protein kinases cAMP-dependent protein kinase, CaM-dependent protein kinases, and C-kinase. A sustained response can be produced by the combined activation either of the cAMP- and CaM-dependent kinases, or of the CaM-dependent kinases and C-kinase. Activation of each type of... 

In addition, a reciprocal interaction between the two phases occurs, in that PKC exerts important feedback effects during the sustained phase of the response. Since activation of PKC leads to an enhancement of calcium efflux and a reduction in the calcium concentration within the submembrane domain, PKC essentially limits its own activity. Furthermore, in adrenal glomerulosa and cultured vascular smooth muscle cells, PKC activation during the sustained phase acts as a feedback modulator of the initial transducing events. The artificial activation of PKC with phorbol esters prevents these initial events (the calcium transient and PIP2 hydrolysis) [59,60] yet at least in cultured smooth muscle cells PI hydrolysis is not blocked [30]. Thus, PKC activation may result in a shift in the substrate specificity of phospholipase C. 

On the basis of results obtained from studies in adrenal glomerulosa, vascular smooth muscle and hepatic cells, it is evident that the major effects of All on cell function are mediated via an activation of the calcium messenger system. Furthermore, the data, although far from complete, provide convincing evidence that a temporal and spatial pattern of events underlies hormonal action. 

Aldosterone production is initiated by 21-hydroxylation of pregnenolone in the adrenal glomerulosa, where there is no 17-hydroxylase activity. The product of hydroxylation of pregnenolone by P450c21 is 21-hydroxy-progesterone, also known as deoxycorticosterone (DOC). The quantity of aldosterone produced by the adrenal is only 1% of that of cortisol for this reason, not all patients with classic P450c21 deficiency manifest with salt wasting. 

Drolet P, Bilodeau L, Chorvatova A, Laflamme L, Gallo-Payet N, Payet MD (1997) Inhibition of the T-type Ca2+ current by the dopamine Dl receptor in rat adrenal glomerulosa cells requirement of the combined action of the G betagamma protein subunit and cyclic adenosine 3, 5 - monophosphate. Mol Endocrinol 11 503-514. 

The release of IP3 from lipids of the plasma membrane is illustrated here by a study involving adrenal glomerulosa cells. Angiotensin was added to the cells at 0 seconds (Figure 10.43). Samples of cells were collected at the indicated times and immediately mixed with acid to halt further metabolism the soluble metabolites were then analyzed- Ihc data illustrate an increase in free intracellular IPS immediately after addition of the hormone. 

The release of Ca from the endoplasmic reticulum and into the cytoplasm is illustrated in another study of adrenal glomerulosa ceils. The cells were incubated... 

FIGURE 10.43 Adrenal glomerulosa cells were incubated in a medium of salts and other nutrients. Inositol was added to the medium. The inositol was radioactive to allow the researcher to determine if metabolism resulted in its incorporation into phospholipids or its modification by phosphorylation. Incubation of [ H]inositol with the cells resulted in its incorporation as phosphatidylpH]inositol diphosphate pH is called tritium). (Redrawn with permission from Balia et al, 1988.)... 

Balia, T., Baukal, A. J., Guillemette, G., and Catt, K. J. (1988). Multiple pathways of inositol polyphosphate metabolism in angiotensin-stimidated adrenal glomerulosa cells. /. Biol. Chem. 263,4083-4091. 

Lang, U., and Vallotton, M. B. (1987). Angiotensin II but not potassium induces subcellular redistribution of protein kinase C in bovine adrenal glomerulosa cells. /. Biol. Chem. 262, 8047-8050. 

There are two distinct subtypes of angiotensin II receptors, designated as type 1 (ATj) and type 2 (AT2). The ATj-angiotensin-II-receptor subtype is located predominantly in vascular and myocardial tissue and also in brain, kidney, and adrenal glomerulosa cells, which secrete aldosterone. 

Quinn, S.J., G.H. Williams D.L. Tillotson. 1988. Calcium oscillations in single adrenal glomerulosa cells stimulated by angiotensin II. Proc. Natl. Acad. Sci. USA 85 5754-8. 

The role of nitric oxide in the regulation of aldosterone synthesis by adrenal glomerulosa cells. J Steroid Biochem Mol Biol 61 47-53... 

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